Analytical system



Oct. 15, 1968 v c. M. FINLEY 3,405,549

ANALYTI CAL SYSTEM fl /dM/f /0 Oct. 15, 1968 c. M. FINLEY 3,405,549

ANALYTICAL SYSTEM Filed Nov. 2, 1964 2 Sheets-Sheet 2 United States Patent O 3,405,549 ANALYTICAL SYSTEM Charles M. Finley, Arcadia, Calif., assignor to Consolidated Electrodynamics Corporation, Pasadena, Calif., a corporation of California Filed Nov. 2, 1964, Ser. No. 408,133 6 Claims. (Cl. 73-23.1)

ABSTRACT F THE DISCLOSURE An analytical instrument combining a chromatographic column, a mass analyzer and an interface circuit. The mass analyzer is arranged to receive and analyze rvarious fractions as they are eluted from the chromatographic column. The interface circuit controls the scanning operation of the mass analyzer responsive to the elution of a fraction from the column.

This invention relates to analytical systems and in particular `to the combination of a gas-liquid chromatograph and a mass spectrometer to accelerate and improve the analysis of complex mixtures as they are separated into their various components and eluted from a chromatographic column.

The basic function of a chromatograph is to separate components of a fluid introduced therein on the basis of their afnity or adsorbability in the partitioning material used in the chromatographic column. In normal use, the results of the analysis by the volumn are indicated by means of peak recorder or integrating device which indicates the number of peaks or fractions in the sample and the relative concentration of each. While a chromatograph is an extremely useful analytical tool, it can not be classied as a truly qualitative instrument because the only method by which a fraction from the column can be identified is a relative one, ie., `by comparing its retention time to the retention time of a known element or compound. The problem is further complicated when two or more compounds have the same or nearly identical retention times.

The resolution of the chromatograph and hence the quality of the analysis is directly dependent upon the partitioning material used and the construction of the column. As more experience has been gathered in the chromatographic art, improvements in the form of advanced column construction and more sophisticated packing and partitioning materials located therein have resulted in substantial improvements in the quality of chromatographic analyses. However, despite these improvements it is normally not possible to obtain complete separation and analysis of complex mixtures of unknown composition since lack of knowledge of sample composition precludes selection of optimum packing. In addition to the problems just enumerated this means that certain fractions from the chromatograph will include more than one component and without further analysis it is impossible to identify the various compounds within this fraction.

A number of solutions have been attempted to this problem, one of them being to collect the fractions as they are eluted from the column. These collected fractions are then subjected to conventional chemical analysis to obtain further qualitative and quantitative information. Such a process is disadvantageous in that it is cumbersome and time consuming and does not lend itself well to rapid analysis, particularly analysis of process streams.

The present invention proposes a solution to this problem by use of a mass analyzer connected to a chromatograph to analyze the various fractions as they are eluted from the chromatograph. The chromatograph and ana- Cil Patented Oct. 15, 1968 ICC lyzer are interconnected by conduit means so that iluid owing from the chromatograph may be passed to the analyzer. In addition, detecting means are provided at the outlet from the chromatograph for sensing a predetermined change in the fluid owing fromthe chromatograph, the mass analyzer commencing operation in response to a signal from the detecting means. Finally, means for introducing a predetermined time delay vbetween the elution of a particular fraction from the chromatograph and the commencement of operation of the mass analyzer are connected between the detecting means and the mass analyzer in order to permit the effluent from the chromatograph to reach the mass analyzer inlet.

Combining a chromatograph and mass anlyzer and providing the attendant circuitry needed to make operation of the various components automatic yield several advantages. Paramount among these advantages are the ability of this analytical system to provide rapid identification and quantitative analysis of simple or complex sample mixtures. In addition to being made completely automatic this system provides this identification and quantitative analysis faster than any other known combination of analytical methods. Furthermore, use of the mass spectrometer as an adjunct to a chromatograph also helps to avoid possible analytical errors when main peaks from the chromatograph are articially enlarged *by impurities.

While the basic arrangement calls for the combination of a chromatograph and a mass analyzer in order to more fully analyze samples introduced into the chromatograph there are in addition to this basic arrangement additional components and a preferred arrangement of these components to yield a fully automatic system. This preferred arrangement comprises a gas chromatograph -with its detector electrically connected to a chromatograph digitizer, an integrating device which has the capability of measuring the quantities of each fraction as the peaks are eluted from the chromatograph. In addition to electrically connecting the detector to the digitizer, the etlluent from the chromatograph is piped to a mass spectrometer. An oscillograph or other chart recorder is connected to the mass spectrometer for recording the results of the analysis.

In normal operation the recorder is not operated continuously nor does the mass spectrometer scan continu ousiy due to the fact that there is frequently a significant time lapse between the elution of adjacent peaks from the chromatograph. Hence it is desirable to coordinate the initiation of scanning by the mass spectrometer and operation of the recorder with the appearance of a peak at the chromatograph output. This is accomplished by inserting in the electrical circuitry between the mass spectrometer scanning electronics and the chromatograph digitizer a circuit which will be referred to herein as an interface circuit. This circuit performs the functions of providing a predetermined time delay between the elution of a peak of interest from the chromatograph and initiation of mass spectrometer scanning to permit the effluent to move over the physical distance from the chromatograph to the mass spectrometer and of starting the mass spectrometer and oscillograph operations when the proper amount of time has elapsed.

The operation of the system and the inter-relation of the various components comprising it will be more fully understood by reference to the following figures in which:

FIG. 1 is a Ablock diagram showing the various components of the system;

FIG. 2 is a typical chromatogram and a mass spectrum of a particular peak or component of the chromatogram; and

FIG. 3 is a schematic of the interface circuit between 3 the chromatograph digitizer and the mass spectrometer scanning electronics.

The inter-relation of the various components of the preferred arrangement of this analytical system are depicted in FIG. 1. In t-hat figure a chromatograph 2 is provided with an inlet 4 in which a sample is introduced by syringe or by various means used to sample process streams. After being carried through the chromatographic column by means of a carrier gas and being subjected to the characteristic differential separation of the chromatograph, the gas sample is separated into a series of fractions which are then passed from the outlet of the chromatograph through a detector 5, usually a thermal conductivity detector, which compares the conductivity of the sample component and carrier gas combination as eluted from the chromatograph with the carrier gas alone. In one method of operation, the electrical output f the detector is fed into a Wheatstone bridge and thence to a chart recorder which records the difference in conductivity between the two gas streams in the form of a series of peaks. However, in the preferred arrangement of the system of this invention there is substituted for the chart recorder a digitizer 12 which reads out directly in numerical quantities, the total quantity of each component present in the sample.

After passing through the detector the sample cornponent and carrier are carried by means of a tubing connection 6 from the outlet of the chromatograph 2 to a stream splitter 7. The stream splitter 7 is a device for limiting the amount of sample introduced to the mass spectrometer inlet since the quantity of sample eluted from the chromatograph usually exceeds that needed by the mass spectrometer. Line 9 from the splitter 7 is normally of capillary size and has a certain constant conductance. The degree of splitting by the stream splitter 7 is a function of the carrier gas flow rate and depends on the chromatographic column used. That portion of the eluent from the chromatograph which is not admitted to the mass spectrometer via line 9 is vented to the atmosphere by the second outlet, line 11, from the stream splitter.

That portion of the stream directed through capillary 9 ows to the mass spectrometer inlet where the amount of sample admitted to the ionization chamber is controlled by means of a valve 3 and pump 13. Such an inlet system is referred to as a continuous-flow capillary system. This system is similar to the constant pressure inlet system described in U.S. Patent 2,569,032 except that the conductance of the inlet leak to the ionization chamber is variable by means of the pump and valve whereas the constant pressure inlet system employs a gold leak which has a constant conductance. Use of a valve and pump instead of a gold leak make it possible to run the source of the mass spectrometer at higher and lower pressures than are possible with a gold leak inlet and thereby provide a means for varying the sensitivity of the spectrometer. The result is a highly versatile analytical system. Since the inter-connections between the chromatograph outlet and spectrometer inlet has a finite length a time delay is inherent between the elution of the component from the chromatograph and arrival at the inlet to the mass spectrometer. Hence the most economical and efcient operation of the system is achieved by delaying the start of mass spectrometer operation until the component arrives at the inlet.

As indicated in FIG. l the electrical output of the chromatograph is fed into a digitizer circuit 12 which performs the function of determining the total quantity of the component under a given peak, as for example, peak 18 in FIG. 2. The digitizer senses the beginning, peak and end of component 18 and is capable of integrating the area under this peak to yield a reading in terms of quantity of component present. Because the digitizer 12 is capable of detecting changes in the slope of peak 18 it is possible to initiate a scan by the mass spectrometer Cil at any significant change in slope in the peak from the chromatograph. Thus it may be desired to cause the mass spectrometer to scan at the beginning or end of peak 18. Normally, however it is preferable that the mass spectrometer scan during the time when the component from the chromatograph is at a peak. This point is preferred because it is here that the sample is at its maximum and most nearly constant concentration thus reducing the possibility of error in the quantitative measurements available from the spectrometer.

Assuming that the circuit is designed to cause the mass spectrometer to scan when the output from the chromatograph is at its peak, the digitizer 12 senses the change of slope (from increasing to decreasing) of peak 18 and pulses a trigger or interface circuit 14. As indicated above, this interface circuit accepts the pulse from the digitizer circuit 12, introduces a certain time delay after the time the pulse is received from the digitizer and subsequently pulses the mass spectrometer electronics 10 to initiate a mass scan. The operation of the interface circuit 14 will be described in more detail below but at this point it is sufiicient to indicate that when the predetermined time delay has expired the interface circuit pulses the mass spectrometer electronics 10 which in turn causes the mass spectrometer 8 to perform a scan over a predetermined mass range and at the same time turns on an oscillograph or other chart recorder 15 for recording the mass spectrum from the mass spectrometer.

A chromatogram 16 representing a typical analysis by means of a chromatographic column is shown in FIG. 2. As that figure depicts, the output from a chromatograph is a series of peaks with each peak indicating one or more components of the sample which have a particular degree of ainity for the partitioning medium in the column. For example, chromatogram 16 could be considered to be an analysis of low boiling hyydrocarbons with peak 18 representing two of these hydrocarbons such as propane and ethylene. Because it is frequently diflicult to determine whether or not a fraction such as peak 18 includes more than one component it is usually necessary to perform further analysis on the component as eluted from the chromatograph in order to definitely determine its composition.

The present invention accomplishes this by funnelling the fraction to a mass spectrometer and initiating a scan by the mass spectrometer of the component at the moment it is introduced to the mass spectrometer inlet. FIG. 2 also illustrates a typical mass spectrum 20 such as would be obtained when the components in peak 18 are analyzed by the spectrometer. As shown in the spectrum, there are a number of secondary peaks and two primary peaks 22 and 24 which indicate the identity of the two compounds present in the peak, viz propane and ethylene. Because the spectrometer has the capability of greater resolution than a chromatograph the advantages of using a mass spectrometer in conjunction with the chromato graph are immediately apparent. By analyzing the fraction as it issues from the chromatograph, the mass spectrometer is capable of further breaking down of the fraction into the various compounds present therein. By combining the indications of both the chromatograph and the mass spectrometer and calibration by comparison to samples of known 'composition a rapid, quantitative and qualitative analysis of a given sample is possible.

FIG. 3 indicates one possible configuration or design of a circuit which is adapted to function as the interface circuit 14 in the block diagram of FIG. 1. In FIG. 3 the output from the digitizer circuit 12 is connected to the interface circuit at terminals 26 and transmitted by means of appropriate passive coupling elements 27 to a silicon controlled rectifier (SCR) 28 which is supplied with battery voltage through dual paths 30 one of which in-` cludes a first relay winding 32. The winding 32 is magnetically coupled to a set of contacts 34 which are operated when current flows through winding 32. The armature 35 of the first relay is electrically connected to the base of transistor 36. This transistor is in turn connected to a second relay Winding 38 which is magnetically coupled to two sets of contacts 40 and 42.

In operation the circuit performs as follows. A positive pulse received from the digitizer circuit 12 is fed into the gate of the SCR 28 which is normally in the off condition. The pulse causes the SCR to conduct thus causing current to flow through relay winding 32 thereby operating contacts 34. The rectifier 28 continues to conduct so long as current ows through winding 32. When contacts 34 of the first relay are closed, current Hows through resistor 44 and charges capacitor 46 thus gradually raising the absolute magnitude of the voltage at the base electrode of transistor 36. Transistor 36 is normally in the nonconducting condition by virtue of the bias applied through Zener diode 48 in the emitter circuit of the transistor. When the voltage buildup on capacitor 46 exceeds the emitter bias voltage, transistor 36 conducts, producing current ow through winding 38 and operation of contacts 40 and 42 of the second relay. Operation of contacts 42 breaks the electrical path to relay winding 32 and the anode of the SCR 28 thus causing the contacts 34 to return to their original state. When contacts 34 return to their unoperated state, capacitor 46 is connected to the battery supply 50 and discharges rapidly through resistor 52 to the supply 50 cutting off conduction of transistor 36 when the base voltage falls below the emitter bias. When transistor 36 is turned off the second relay returns to its original state and the SCR 28 remains off until triggered again.

It is the closure of contacts 40 of the second relay which is used to trigger the scan circuit to the mass spectrometer. When the scan is completed the mass spectrometer and oscillograph are arranged to automatically shut ot until triggered again by the interface circuit. Note that the closure of these contacts follows at some given time interval after the closure of the contacts of the first relay. This time delay is the desired delay to permit the component to be analyzed to pass from the chromatograph to the mass spectrometer. The time elapsing after the impulse is received at terminals 26 until the closure of contacts 40 occurs is adjusted by varying resistor 44.

While the operation of the interface circuit of this particular system is electronic it is equally possible that the same functions can be accomplished by pneumatic or hydraulic mechanisms. Furthermore it is also not essential that a digitizer circuit be used. In place of it a simple peak detector may be substituted which can be driven by the output of the chromatograph or if desired by the mass spectrometer itself. In this latter case it is possible to use the output of the pressure gauge of the mass spectrometer or an indication from the mass spectrometer tube. When an output of the mass spectrometer tube is used a typical scheme of operation would be to cause the mass spectrometer to operate continuously but only to monitor for occurrence of a specific mass. Then when the specific mass is encountered the output from the mass spectrometer tube can be transmitted to the mass spectrometer electronics causing the mass spectrometer to switch from monitoring to scanning of a given mass range. When operated in this fashion the mass spectrometer tube or the pressure gauge can themselves be thought to yield a special type of chromatogram.

The result is a new analytical system which enhances the operation of a chromatograph by means of a mass spectrometer and other components integrated into a single automated system to perform quantitative and qualitative analyses on gases, liquids and low melting organic samples. Such a device is suitable not only for quality control but also for identification of process streams whose exact composition has heretofore been unknown.

I claim:

1. An analytical system comprising a chromatograph for separating a sample introduced therein into a plurality of fractions and issuing the fractions therefrom sequentially, a mass analyzer including mass scan initiating means connected to the chromatograph for separating a fraction from the chromatograph according to the mass of the compounds present in the fraction, means for detecting the presence of a fraction issuing from the chromatograph connected to the mass scan initiating means for commencing a mass scan operation of the mass analyzer in response to an indication from the detecting means.

2. An analytical system comprising a gas chromatograph for separating a fluid sample introduced therein into a series of fractions, a detecting means connected to the chromatograph, a mass analyzer for separating a sample introduced therein according to its component masses, the mass analyzer including means for initiating a mass analysis in response to the occurrence of a predetermined output from the detecting means, means connecting the chromatograph outlet to the mass analyzer so that fluid owing from the chromatograph may be passed to the analyzer inlet and means connecting the detecting means and the mass analysis initiating means for introducing a predetermined time delay between the occurrence of the predetermined output from the detect* ing means and the initiation of a mass analysis to permit a fraction from the chromatograph to reach the mass spectrometer inlet.

3. An automatic analytical system comprising a gasliquid chromatograph for separating a uid sample introduced therein into a series of fractional peaks, a detecting means electrically connected to the chromatograph, the detecting means having the capability of sensing a change in the slope of the chromatograph peaks, a mass spectrometer inc'luding means for initiating a mass scan, conduit -means connecting the chromatograph and mass spectrometer for flowing =a portion of a peak from the chromatograph to the mass spectrometer, a -recorder electrically connected to the output of the mass spectrometer and an interface circuit electrically connected between the detecting means and the mass scan initiating means and recorder for causing the mass spectrometer and recorder to operate in response to an output from the detecting means after introducing a predetermined time delay :between the occurrence of the output of the detecting means and operation of the mass Spectrometer and recorder to permit a peak from the chromatograph to reach the mass spectrometer inlet.

4. An automatic analytical system comprising a gasliquid chromotograph for separating a gas sample introduced therein into a series of fractional peaks, an integrating means electrically connected to the chromatograph output, the integrating means having the capabilities of sensing a change in the slope of the chromatograph peaks and of quantitatively measuring the various outputs from the chromatograph, a mass spectrometer for separating a sample introduced therein into its component masses and including means for initiating a mass scan, conduit means connecting the chromatograph outlet to the mass spectrometer inlet for flowing a portion of a peak from the chromatograph to the mass spectrometer, a recorder electrically connected to the output of the mass spectrometer and an interface conduit electrically connected between the integrating means and the mass scan initiating means and recorder for causing the mass spectrometer and recorder to commence operation in response to an output from the integrating means after introducing a predetermined time delay -between the occurrence of the output of the integrating means and operation of the mass spectrometer and recorder to permit a peak from the chromatograph to reach the mass spectrometer inlet.

5. An analytical system comprising a chromatograph, a mass analyzer including means for initiating a mass scan, means interconnecting the chromatograph and analyzer so that uid owing from the chromatograph may be passed to the analyzer, detecting means for sensing a predetermined change in the fluid flowing from the chromatograph connected to the mass scan initiating means for causing the analyzer to commence a scanning operation in response to a signal from the detecting means, the analyzer performing a mass separation of a portion of the fluid from the chromatograph.

6. An analytical system comprising a chromatograph 10 for separating a uid sample introduced therein into a series of fractions and issuing the fractions therefrom in sequence, a mass analyzer including Imeans for initiating operation of the mass analyzer for separating samples References Cited UNITED STATES PATENTS 3,245,269 4/1966 Ivie F/3-23.1 XR 3,291,980 12/1966 Coates et al 73-23.1 XR 3,301,040 1/1967 Levy et al. 73-23.1

OTHER REFERENCES Banner et al.: Gas Chromatography-Brighton, 1964, Goldup, pp. 180-189.

Ryhage: Analytical Chemistry, vol. 36, No. 4, April introduced into the analyzer according to the mass of 15 1954, pp 759 764 each compound present in the sample, means for transporting the chromatographically separated fractions to the mass analyzer inlet and means for detecting the presence of a fraction issuing from the chromatograph RICHARD C. QUEISSER, Primary Examiner. C. A. RUBI-IL, Assistant Examiner. 

